Emergency Department Management of North American Snake Envenomations (Trauma CME and Pharmacology CME)

Emergency Department Management of North American Snake Envenomations (Trauma CME and Pharmacology CME)

Venomous native North American snake families include the pit vipers (copperheads, water moccasins/cottonmouths, and rattlesnakes) and coral snakes. Pit viper venom is coagulopathic, and coral snake venom is neurotoxic – so what are the differences in ED management between the 2 types of envenomations? This issue reviews the best evidence behind some of the conflicting recommendations, local practices, and “folklore” surrounding snakebites:

• Ice, pressure immobilization, incision and suction: are they still recommended?
• How can you tell whether - and how much - venom was injected?
• Why you must mark and time edema and erythema from a snakebite
• What can antivenom do - and not do?
• What are the antivenom options for coral snake bites?
• When is airway compromise a concern, and will antivenom reverse it?
• Is there a greater risk for anaphylaxis from the snakebite or the antivenom?
• What is the likelihood of bleeding days or weeks after a snakebite?
• What are the different observation time recommendations, based on type of snake and bite severity?

Abstract

There are approximately 10,000 emergency department visits in the United States for snakebites every year, and one-third of those involve venomous species. Venomous North American indigenous snakes include species from the Crotalinae (pit vipers) and Elapidae (coral snakes) subfamilies. Treatment relies on supportive care, plus antivenom for select cases. While certain principles of management are widely accepted, controversies exist with regard to prehospital use of pressure immobilization, antivenom use, coagulation testing after copperhead envenomation, and fasciotomy. An evidence-based approach to management of North American venomous snakes will be discussed, along with a review of the current controversies.

Case Presentations

A 4-year-old boy is brought to your ED by his distraught parents. An hour ago, he was in the backyard by the pool, playing with what they thought was a toy. He started screaming, and when the mother moved closer, she saw a foot-long black, yellow, and red snake in his hand. She frantically pulled it off him and threw it into the bushes. She reports that she had to pull quite hard before it would release. The child has several small marks on the palm of his left hand. There is minimal redness, and no swelling is apparent. The dad took a picture of the snake with his phone and you can tell quickly that it was a coral snake. The child is asymptomatic currently, but the nearest pediatric ICU is over an hour away. You wonder: should you transfer this patient to the ICU or can you observe him in the ED—and should you start antivenom?

A 26-year-old man arrives to the ED via private vehicle with his arm in a makeshift sling. He reports that his pet rattlesnake bit him on his right index finger about 45 minutes ago. His hand and wrist are swollen. He reports that he has no past medical history besides his 3 previous visits for snakebites. He reports having a “reaction” to the snakebite antidote during his last visit. You wonder whether the patient is immune . . . or should you give antivenom again?

A 51-year-old man with a history of a rattlesnake bite approximately 4 days ago presents from his primary care physician's office for abnormal lab test results. He reports easy bruising and some bleeding when he brushes his teeth, but is otherwise asymptomatic. You wonder how you should manage this patient.

Introduction

According to the American Association of Poison Control Centers (AAPCC) 2006-2015 annual reports, there were 65,695 reported exposures and 31 deaths from snakes in the United States in that time period.1 There are 2 subfamilies of venomous snakes that are native to the United States: (1) the Crotalinae (pit vipers, subfamily of family Viperidae), which includes rattlesnakes, copperheads, and water moccasins (also called cottonmouths), and (2) the subfamily Elapidae (subfamily of family Colubridae) of which only the coral snake is native to the United States. Bites from snakes from these native subfamilies can produce significant morbidity and, rarely, death, so prompt clinical evaluation and management is essential. In addition, exotic snakes are popular as pets, and bites from these snakes may cause rapid death, depending on the species, so expertise is required to manage them expeditiously.

Patients with snake envenomations generally access healthcare either through the emergency department (ED) or through first-aid providers who generally turn to the emergency clinician for direction. Management of envenomations is considered a core competency of emergency clinicians, and along with Poison Control Centers, they often serve as community resources for snakebite emergencies. Not all envenomations require antivenom; however, delayed administration may lead to significant morbidity and even death, in some cases. This issue of Emergency Medicine Practice provides a comprehensive update on the principles of clinical evaluation of envenomations from pit vipers and coral snakes native to the United States as well as current management recommendations and controversies. Resources are also provided to assist in the management of envenomation from exotic species.

Critical Appraisal of the Literature

A literature search was performed on PubMed using the search terms snake bites, snake envenomation, Agkistrodon, cottonmouth, copperhead, rattlesnake, Crotalinae, Elapidae, Colubridae, water moccasin, coral snake, and pit viper. A total of 120 relevant articles from 2006 to 2017 were reviewed.

A search of literature published from 2006 to 2017 using key terms snake bite or snake envenomation of the Cochrane Database of Systematic Reviews, Evidence Based Medicine Reviews: Best Evidence (ACP), Database of Abstracts of Reviews of Effectiveness (DARE), and Evidence-Based Medicine Reviews Multifile (EBMZ) identified 11 articles. Of these, 3 were not relevant to indigenous North American snakes, 3 were randomized controlled trials, 1 was a poststudy subanalysis, and 2 were reviews (Cochrane and DARE).

As is the case with most of the toxicology literature, evidence on the management of snake envenomations from high-quality prospective randomized controlled trials is limited. The few published studies in the past 10 years are mostly from other countries where the snake species, the level of supportive care, and antivenom availability and effectiveness are different from that in North America. The literature is comprised primarily of case reports/series, retrospective chart reviews, animal model studies, expert consensus panels, and review articles.

The current relevant literature is comprised of case reports/series describing novel or known but not well-characterized clinical effects after a snake envenomation; observational studies using data from hospital charts, Internet search, Poison Control Centers, and national databases; animal model studies; in vitro venom and antivenom studies; conclusions from expert consensus panels; a position statement; and 3 randomized controlled trials. Many of the retrospective observation studies utilized Poison Control Center data (Texas Poison Control Center Network, Florida Poison Information Center Network, AAPCC database, and the American College of Medical Toxicology ToxIC North American Snakebite Registry). Poison Control Centers collect self-reported, unverified information provided by the public or healthcare workers on potential or actual exposures, but they may not be true envenomations and may not reflect the true incidence of snakebites. Furthermore, reported clinical effects and outcomes may be incomplete or inaccurate. For example, according to a compilation of data reported to United States Poison Control Centers, there were no deaths from coral snakes from 2006 to 2015; however, a confirmed death after a coral snake envenomation was published in 2009 (the first and only confirmed death in the literature).2 The ToxIC Registry contains prospectively collected verified clinical information, and it also relies on voluntary reporting.

Most of the management recommendations discussed in this article are based on expert opinion supported by low- to moderate-quality evidence. Expert consensus panel recommendations for the surgical management of snake envenomation were published in 2013.3 Clinical questions were structured in the “Patient, Intervention, Comparison, Outcome” format, and recommendations were developed using Grading of Recommendations, Assessment, Development, and Evaluation. A unified treatment algorithm for the management of Crotalinae envenomations was published in 2011.4 Experts utilized a modified Delphi methodology to develop evidence-informed recommendations. Standard evidence-level scales were not used, as only 1 randomized clinical trial involving the treatment of Crotalinae envenomation with antivenom had been published at the time.5 Since then, a randomized clinical trial comparing Crotalidae Polyvalent Immune Fab (Ovine) (FabAV, CroFab®) to F(ab’)2 immunoglobulin derivatives was published in 2015.6 Additionally, a post hoc analysis of data from this trial comparing copperhead coagulation parameters was also published.7 A position statement from leading national and international clinical toxicology associations regarding use of pressure immobilization after a North American Crotalinae snake envenomation was published in 2011.8

1. “The patient had some minor abrasions, but no visible fang marks, pain, or swelling at the bite site, so I discharged him.”

Patients can develop a coagulopathy and covert bleeding from pit viper bites without having visible tissue damage. The patient should be observed for a minimum of 8 hours, and coagulation studies repeated before discharge home. Coral snake bites may not produce any visible signs on examination. If a coral snake is the suspected culprit, the patient should be monitored for 24 hours to ensure delayed symptoms do not develop.

3. “I thought that I could wait until signs of respiratory distress developed, because the antivenom would quickly reverse the paralysis.”

Administration of antivenom does not reverse symptoms; it merely halts progression of symptoms. Patients with coral snake bites should be treated with antivenom at the first signs of neurological impairment.

7. “The patient had urticaria and wheezing that developed soon after I started administering antivenom, so I stopped the infusion. The patient continued to worsen, even though I stopped it.”

Allergic reaction to antivenom is a serious adverse effect; however, patients can also develop anaphylaxis and other allergic symptoms to snake venom. For each case, consider this possibility and weigh the risks of not treating a snakebite. Consultation with a regional Poison Control Center is recommended.

Tables and Figures

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References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

American College of Medical Toxicology, American Academy of Clinical Toxicology, American Association of Poison Control Centers, European Association of Poison Control Centres and Clinical Toxicologists, International Society on Toxinology, Asia Pacific Association of Medical Toxicology. Pressure immobilization after North American Crotalinae snake envenomation. Clin Toxicol (Phila). 2011;49(10):881-882. (Position statement)

Pit vipers—rattlesnakes, copperheads, and water moccasins/cottonmouths—produce a predominantly hemotoxic venom. Both local and systemic effects can occur. Systemic effects include tachycardia, tachypnea, hypotension, nausea, vomiting, weakness, and diaphoresis.

Patients with snakebite should be treated with supportive care, pain control, and specific antivenom, when indicated.

American College of Medical Toxicology, American Academy of Clinical Toxicology, American Association of Poison Control Centers, European Association of Poison Control Centres and Clinical Toxicologists, International Society on Toxicology, Asia Pacific Association of Medical Toxicology. Pressure immobilization after North American Crotalinae snake envenomation. Clin Toxicol (Phila). 2011;49(10):881-882. (Position statement) DOI: https://doi.org/10.1007/s13181-011-0174-2

Nachi: Although this isn’t something we encountered too frequently – it does seem like I’ve been hearing more about snake bites in the recent months.

Jeff: I actually flew someone just the other day because the local ED ran out of CroFab after an envenomation in Western PA.

Nachi: Yeah, this is definitely more than “just a boards topic,” and it’s really important to know about in those rare circumstances. In terms of incidence, there are actually about 10,000 ED visits in the US for snake bites each year, and 1/3 of these involve venomous species.

Jeff: That’s a good teaser, so let’s start by recognizing this month’s team – the two authors, Dr. Sheikh, a medical toxicologist, and Patrick Leffers, a pharmD, and emergency medicine and clinical toxicology fellow. Both are at the University of Florida Jacksonville, and they reviewed a total of 120 articles from 2006-2017, in addition to reviews from both Cochrane and Dare.

Nachi: And don’t forget our peer reviewers this month, Dr. Daniel Sessions, a medical toxicologist working at the South Texas Poison Center, and our very own editor-in-chief, Dr. Andy Jagoda, who is also Chair of the Department of Emergency Medicine at Mount Sinai in New York City.

Jeff: What a team! But, let’s get back to the snakes. As some background, from 2006-2015 there were almost 66,000 reported snake exposures and 31 deaths from snake envenomations in the US. Of course, this number likely underestimates the true total.

Nachi: And there are two key subfamilies of venomous snakes to be aware of – the Crotalinae – or pit vipers – which includes rattlesnakes, copperheads, and water moccasins; and the Elapidae – of which you really only need to know about the coral snake.

Jeff: And while those are the only two NATIVE snake subfamilies to be acutely aware of, don’t forget that exotic snakes, which are shockingly popular pets -- they can also cause significant morbidity and mortality.

Nachi: Oh, and one other quick note before we get into the epidemiology – most of the recommendations this month come from expert opinion, as high quality RCTs are obviously difficult. In addition, many of the studies were based in other countries, where the snakes, the anti-venoms and their availability, and the general healthcare systems are different from those that most of us work in.

Jeff: Unless we have listeners abroad? Do we have listeners in other countries?

Nachi: Oh we definitely do... but we are going to be a bit biased towards US envenomation today. In any case, venomous snake bites occur most frequently in men aged 18 to 49 during warmer months with provoked bites occurring more frequently in the upper extremities and unprovoked bites in the lower extremities.

Jeff: In one study of poison center data from the last decade, nearly half of all victims of snake bites were victims of unknown type snakes. However, of those that were known, copperheads were the most common, while rattlesnakes caused the most fatalities – 19 of 31 in this dataset.

Nachi: In a separate study of snake bites in the early 2000s, 32% of exposures were from venomous snakes and 59% of those resulted in admission. That’s remarkably high.

Jeff: Snake bite severity depends on several key factors: the amount of venom, the composition of the venom, the body size of the bite victim, the victim's clothing, the size of the bite, comorbid conditions, and the timing and quality of medical care the victim receives.

Nachi: To be a bit more specific - First, the amount of venom will depend on the species of snake, with variations even occurring within the same species. Secondly, while there is a correlation between rattlesnake size and bite severity, there is much more at play. Some snakes can even vary the amount of venom based on threat risk – with defensive bites having different profiles than bites to strike prey.

Jeff: I found it pretty interesting that an estimated 10-25% of pit viper bites are considered dry bites, that is, ones in which no venom is released.

Nachi: Right, this is just one reason why all victims shouldn’t immediately get anti-venom, but we’ll get there.

Jeff: We definitely will. As we already stated – venom composition varies greatly. Pit vipers produce a predominantly hemotoxic venom. Systemic effects include tachycardia, tachypnea, hypotension, nausea, vomiting, weakness, and diaphoresis. Neurotoxicity is rare and is usually due to inter-breeding between species.

Nachi: While rattlesnake bites are associated with higher morbidity and mortality, the more common copperhead bites typically only cause local tissue effects. More serious systemic findings such as coagulopathy and respiratory failure have been reported though.

Jeff: So that’s a solid background to get us started. Let’s talk about the individual snakes. Why don’t you start with the crotalinae family – aka the pit vipers.

Nachi: Sure – the crotalinae includes rattlesnakes, cottonmouths (also known as water moccasins), and copperheads. These make up the vast majority of reports to the poison centers. They can be identified by their heat sensing pits located behind their nostrils (hence pit vipers). As a general rule, you can also identify the venomous snakes by their triangular or spade-like head, elliptical pupils, and hollow retractable fangs.

Jeff: Wait, so you want me to walk up to the snake and ask to see if their fangs retract… yea, no thanks.

Nachi: Haha, of course not, I’m just giving you some of the general principles here. In contrast, non-venomous pit vipers have rounded heads, round pupils, a double row of vertical scales, and they lack fangs.

Jeff: In terms of location, rattlesnakes are found in all states but Hawaii, and cottonmouths and copperheads are distributed mostly throughout the southern and southeastern states, with copperheads also extending further north, even into Massachusetts.

Nachi: Moving on to the Elapidae – there are 3 species of coral snakes, only two of which you need to know about, Micrurus fulvius fulvius or the eastern coral snake and Micrurus tener or the Texas coral snake. Of the two, the eastern or Micrurus fulvius fulvius produces more potent venom.

Jeff: As you may have guessed by their names, the eastern coral snake is found in the southeastern united states, specifically, east of the Mississippi -- whereas the Texas coral snake lives west of the Mississippi.

Nachi: Venomous North American coral snakes can be recognized by the red and yellow bands around their bodies whereas their nonvenomous counterparts can be recognized by their characteristic black band between the red and yellow bands. I’m sure you’ve heard the popular mnemonic for this… Red touch yellow kill a fellow, red touch black, venom lack.

Jeff: I have heard that one, and it’s not a bad mnemonic. Just remember that this is more of a guideline than a rule, as it doesn’t always hold true.

Nachi: Coral snakes also tend to chew rather than bite thanks to their short, fixed, hollow fangs. Locally, bites can lead to muscle destruction thanks to a certain myotoxin. Systemic signs of infection include nausea, vomiting, abdominal pain, and dizziness.

Jeff: The venom also contains a neurotoxin which can lead to diplopia, difficulty swallowing and speaking and generalized weakness.

Nachi: Complicating matters even further, the onset of these symptoms may be delayed for many hours.

Jeff: Alright, so I think that about wraps up the background. Let’s move on to the meat and potatoes of this article, starting with the differential.

Nachi: For differential this month, we are really focusing on differentiating a venomous snake from a non-venomous one.

Jeff: Oh yeah, this is where you want us to ask the snake if it can retract its fangs, right?

Nachi: Ha very funny – Although the type of snake may be obvious if the patient owns the snake, for most cases you see in the ED, the type of snake won’t be clear. Try to get a description of the snake and consider your local geography. Some patients may even bring the snake in with them.

Jeff: yea, no thanks. As for prehospital care, it’s actually pretty interesting stuff as recommendations have changed many times. You may have heard of the recommendations for incision / excision, use of venom extraction devices, tourniquets, chill methods and even electroshock therapy – well these methods are all OUT.

Nachi: Not only are they out, they actually worsen outcomes, so definitely don’t pursue any of them. Instead, since no treatment has been shown to improve outcome, you should prioritize prompt transport.

Jeff: And while we definitely don’t want to encourage ill-advised attempts at capturing the snake, taking pictures at a distance may be helpful in identifying it. Oh and the authors do note- pretty terrifying stuff coming up here so brace yourself - even if the snake is dead the bite reflex is still intact…

Nachi: And that’s why I work in city hospitals…

Jeff: There’s also a bit of controversy here with regards to pressure immobilization, which is definitely something I thought we were supposed to do in the prehospital setting. Apparently in other countries, like Australia, prehospital providers frequently employ pressure immobilization – that is, wrapping bandages proximally up a splinted limb to impede lymphatic toxin spread.

Nachi: Right, but in Australia, not only are the snakes more venomous but the hospital transport distances are much longer, so, basically they sacrifice the limb to potentially save a life. In the US, with our current indigenous snake population and the relatively short transport distances, this isn’t justified at all!

Jeff: Take home: based on the current literature, the American College of Medical Toxicology, other experts, and Drs. Sheikh and Leffers recommend against pressure immobilization in lieu of prompt patient transport to definitive treatment.

Nachi: Good to know – alright so now we have the patient in the emergency department, let’s begin ED care. As always – IV, O2, Monitor including end tidal CO2 if you suspect a neurotoxic or exotic snake bite. Of course, avoid using the affected limbs for vitals…

Jeff: If not done already, remove any constrictive clothing or jewelry and mark the leading edge of pain, edema, and erythema both above and below the bite. If EMS has placed bandages, leave them in place until antivenom and resuscitative equipment is ready.

Nachi: And definitely involve the poison control center or a medical toxicology service early as they are an amazing resource. It’s an easy number to remember.. 1-800-222-1222. If you just type “poison control center” into google, that number will come up immediately.

Jeff: Hypotension should be treated with isotonic fluids and, as usual, anaphylaxis should be treated with the usual cocktail of antihistamines and epinephrine at first IM and then via infusion if refractory. Note that antivenom will NOT reverse anaphylaxis on its own.

Nachi: When eliciting a history, there are a number of important factors to look out for, including – time and location of the bite, description of the snake, tetanus status, comorbid conditions, medications and allergies, any systemic or neurologic symptoms, muscle cramps, perioral tingling or numbness, metallic taste, history of previous snakebites and any reactions to previous envenomation or antivenom treatment.

Jeff: Moving on to the physical exam, when examining the wound, look specifically for local tissue effects which occur in over 90% of patients after pit viper envenomations. In such cases, you would expect pain, erythema, swelling, tenderness, and myonecrosis beginning at the wound site and then spreading via the lymphatic system.

Nachi: In addition, specifically with pit viper envenomations, monitor the patient for possible compartment syndrome as the venom can lead to local tissue destruction, increased cell permeability, third spacing of fluids, and bleeding. And remember that while the local compartment may be hypertensive, the patient may also have systemic hypotension.

Jeff: Just to reiterate what I said before –[DING SOUND] hypotension may indicate severe anaphylaxis and its not necessarily just due to third spacing. Regardless, the treatment is the same – epinephrine.

Nachi: Good point, but let’s focus on compartment syndrome for a minute. True compartment syndrome is actually quite rare --- its really subcutaneous hypertension with preservation of otherwise normal compartment pressures that you’re most likely to see. Compartment syndrome should therefore only be diagnosed by actual compartment measurements and not just the exam. However, if you are dealing with compartments that can’t be measured, like in the fingers, you’re only choice is to be guided by the exam…

Jeff: Risk factors for compartment syndrome in the setting of a snake bite include envenomations in small children, involvement of digits, application of ice or cold packs, and delayed or inadequate antivenom administration.

Nachi: In terms of respiratory effects of envenomations – they aren’t common. Both bites to the head or neck and neurotoxin containing venom are potential causes. In the setting of respiratory failure, be prepared with advanced airway maneuvers like nasotracheal intubation or cricothyroidotomy. Antivenom will not reverse respiratory failure.

Jeff: Neurologic effects may be present upon arrival but may also be delayed up to 12 hours in the case of eastern coral snake bites.

Nachi: It’s noteworthy that in one study of almost 400 eastern coral snake exposures, the onset of systemic symptoms occurred on average 5.6 hours after the bite. So definitely remember that repeat exams and observation will be tremendously important.

Jeff: The actual neurologic symptoms to look for depend on the snake. Coral snake venom can produce a descending flaccid paralysis characterized by motor weakness, especially of the cranial nerves. Similarly pit vipers, especially the Mojave rattlesnake, have also been associated with muscular weakness of the cranial nerves and even respiratory insufficiency.

Nachi: Pit viper envenomation can also lead to myokymia which is repetitive small muscle fasciculations. [DING SOUND] Unfortunately, this myokymia may not respond to antivenom administration and myokymia of the chest well and torso can necessitate intubation in extreme cases. Both myokymia and myonecrosis may lead to rhabdo in the case of significant envenomations.

Jeff: Pit viper envenomation can also cause hematologic effects. Fibrinolysis and platelet consumption at the bit site can lead to decreased fibrinogen and thrombocytopenia. In severe cases this can lead to systemic bleeding and even hemorrhagic shock. Those on anticoagulants and anti-platelet agents are at increased risk.

Nachi: Dermal effects such as edema, ecchymosis, bullae, and bleeding are not uncommon, but up to 50% of coral snake bite victims may have none of these.

Jeff: And to round out this section – just be aware that rare effects such as osteonecrosis, ischemic stroke, massive PE, and septic shock have all been reported.

Nachi: Let’s move on to diagnostic studies. Most patients require a CBC, coags, and a fibrinogen concentration. Those with systemic toxicity should also have their electroyltes, CPK, creatinine, glucose, and urine tested.

Jeff: And while the data is somewhat mixed, one study suggests that all patients with pit viper envenomations need their coags checked, not just those with severe symptoms as in one series nearly 90% of patients had missed coagulation abnormalities. The clinical consequences of this aren’t clearly explained, so the authors don’t make a specific recommendation.

Nachi: In terms of imaging, a chest x-ray should be obtained in those with respiratory symptoms and ultrasound may even have an expanding role here for tracking edema, looking for fluid collections, and assessing deep muscle compartments and vascular flow.

Jeff: I feel like we should get some entry music for every ultrasound reference because it seems to make its way into just about every episode.

Nachi: What would it sound like? You bring this up every month. I’ll look into something for a future episode. If any of our listeners have a suggestion, shoot us an e-mail at EMplify@ebmedicine.net. In terms of monitoring and observation, this is important, ALL patients with suspected pit viper envenomations should be observed for 8-12 hours with the leading edge marked every 15-30 minutes.

Jeff: In addition, serial diagnostic testing may also be needed as such changes will be used to guide treatment. In those with systemic symptoms, lab testing will be required every 4-6 hours prior to discharge.

Nachi: Before we move onto treatment – let me quickly mention grading. There is no universal grading system. The snakebite severity score, the minimum-moderate-severe score, and grade 1-4 score which consider symptoms, exam findings, and lab abnormalities have all been studied. None have been validated and none track changes, so the authors recommend relying on severity of symptoms and progression of symptoms to guide treatment.

Jeff: The crux of treatment for pit viper envenomations is with supportive care and anti-venom.

Nachi: FabAV or CroFab is the antivenom of choice for pit viper envenomations. This antivenom is made from extracting the Fab portion of anti-venom antibodies from envenomated sheep and processing them with papain.

Jeff: Since the sheep are injected with venom from the western diamondback, eastern diamondback and Mojave rattlesnake as well as the cottonmouth, the FabAV is most effective against venom from these snakes, however it does have cross reactivity to other immunologically similar venoms.

Nachi: Indications for FabAV include a more than minimal local swelling, rapid progression of swelling, swelling crossing a major joint, evidence of hemotoxicity, signs of systemic toxicity including hemodynamic compromise, neuromuscular toxicity, and late or recurrent new-onset coagulopathy.

Jeff: Initially, dose FabAV as a bolus of 4-6 vials, IV. With life threatening envenomations or those with cardiovascular collapse, double the starting dose to 8-12 vials. The goal is arresting progression, improvement in coagulation abnormalities, and resolution of systemic symptoms.

Nachi: Although FabAV will reduce the duration and severity of symptoms and lab abnormalities, it will not reverse tissue necrosis and may not reverse neurologic effects.

Jeff: Once the symptoms have been controlled after the bolus dose or a second bolus dose, maintenance dosing of 2 vials every 6 hours for 3 doses is recommended to prevent recurrence.

Nachi: So to reiterate. 4-6 vial bolus to start, doubled in severe cases and then 2 vials every 6 hours for 18 hours after that.

Jeff: You got it.

Nachi: And like most, maybe all medicines, there are side effects and contraindications to be aware of. Hypersensitivity reactions and serum sickness to FabAV have been reported as 8% and 13% respectively. Most are mild and can be treated with your standard bundle of steroids, antihistamines, fluids and epi.

Nachi: Although FabAV isn’t produced using copperhead venom, it may be effective in severe envenomations and in one study, FabAV reduced limb disability compared to placebo.

Jeff: Therefore, the authors very reasonably advise that you should use the patient’s clinical picture and individual factors rather than the snake species to guide your treatment.

Nachi: Interestingly, compartment syndrome should be treated with the initial 4-6 vial dose of antivenom and not necessarily a fasciotomy. Fasciotomies have not been shown to improve outcomes and are reserved only for those failing anti-venom treatment.

Jeff: The reason for this is that antivenom may reduce tissue pressures obviating the need for fasciotomy. In addition, fasciotomy wouldn’t affect muscle necrosis that is occurring so fascia removal really doesn’t solve anything.

Nachi: And just as anti-venom can be used to treat elevated compartment pressures, it can also be used to treat coagulopathy.

Jeff: Blood products should be used for those who are actively bleeding or severely anemic as venom does not discriminate and will destroy whatever blood it comes across.

Nachi: Recurrent and late onset coagulopathy after FabAV treatment has also been well described. Although not exactly clear why, some speculate that it occurs for one of 4 reasons. 1) because the half life of FabAV is shorter than that of the venom, or 2) because the venom is initially stored in the soft tissues and then slowly released over time or 3) because the venom has a late onset component, or lastly, 4) there is delayed dissociation of the venom-antivenom complexes. Regardless of the mechanism, late onset coagulopathy can be treated with FabAV.

Jeff: Luckily, bleeding associated with coagulopathy and bleeding associated with late onset coagulopathy are both extremely rare.

Nachi: Moving on to coral snakes. Coral snake bites should be treated with NACSA or North American Coral Snake anti-venim. This antivenom halts or at least limits the progression of muscle paralysis and shortens the clinical course.

Jeff: Most experts recommend NACSA treatment with the first signs of systemic toxicity and not for all comers. This recommendation is backed by the literature as in one observational study those treated with prophylactic NACSA did less favorably as compared to those who got it only after symptoms onset. This is probably because NACSA doesn’t reverse neuromuscular weakness and only limits progression.

Nachi: And it’s not like you are just sitting by and watching while doing nothing – focus your initial treatment on wound care, pain control, and then observation for the development of systemic symptoms. The exact length of observation will depend on the snake, but should be somewhere between 8 and 24h.

Jeff: As for dosing – the initial NACSA dose is 3-5 vials IV for both peds and adults with a repeat dose if the initial symptoms don’t improve.

Nachi: Side effects and adverse reactions occur somewhere between 8-11% of the time with dermal reactions being most common and anaphylaxis being the most severe.

Jeff: There is also one last anti-venom to be aware of – Coralmyn, for coral snake envenomations. Coralmyn is a polyclonal antivenom F(ab’)2 coral snake antivenom, developed because the current lot of NACSA has technically expired although the date has been extended numerous times. It’s currently in a phase 3 trial, so keep your eyes out.

Nachi: Other non-antivenom treatments that have been tested include acetylcholinesterase inhibitors and trypsin at the bite site – both should be considered experimental at this point.

Jeff: To wrap up the treatment section, let’s talk exotic snakes. You may recall from the intro that these have a higher morbidity and mortality compared to native species.

Nachi: You will have to rely on your local poison control center or toxicologist for advice and you may even need to turn to the zoo or aquarium for antivenom, if it exists at all. Patients with bites from exotic snakes should be monitored, likely in the ICU, for up to 24 hours as toxicity from some venom may have a delayed onset of up to 20 hours.

Jeff: Scary stuff, hopefully the patient knows which type of exotic snake they own and you don’t have to sort through a million google images to try to get to the bottom of this. Anyway, there are 3 special populations to discuss. First are pregnant patients.

Nachi: The authors cite a 1.4% incidence of snake bites in pregnant patients. They note that this is low, but from my perspective, this seems shockingly high – why would a pregnant person ever get anywhere near a snake, seems just ill advised…

Jeff: haha, true. But regardless, treatment is the same with antivenom as needed for all the same indications. With fetal demise rates as high as 30%, in addition to maternal monitoring, the fetus should also be monitored.

Nachi: That number may seem high, but keep in mind that that’s from studies in other countries with more venomous snakes, so it’s likely to be lower in the US. But the point remains, that antivenom is generally recommended to be given if the mother has indications for treatment, as poor fetal outcome is tied directly to the severity of envenomation in the mother.

Jeff: Continuing right along, the next special population to discuss are pediatric patients. Because dosing is based on the amount of venom delivered and not on patient specific factors, dosing is the same for peds and adults.

Nachi: How rare – so few meds seem to be the same for peds and adults. The last population to discuss are anticoagulated patients. Patients on antiplatelet or anti-coagulants are at increased risk of bleeding after pit viper envenomations and therefore should have their coags checked every 2 days following the last dose of FabAV.

Jeff: I think we’ve at least mentioned most of this months controversies, but it’s probably worth quickly reviewing them since they mostly dispel common myths.

Nachi: Good idea. Incision and suction of snake bites is nearly universally not recommended.

Jeff: In the absence of ischemia, fasciotomy for snake bites is not recommended, even with elevated compartment pressures. Instead treat compartment syndrome with anti-venom and save the fasciotomy for true cases of ischemia refractory to antivenom.

Nachi: With a known or suspected coral snake envenomation, due to shortages of NACSA, wait until the patient develops symptoms instead of empirically treating all bite victims.

Jeff: Maintenance dosing of FabAV continues to be debated. The manufacturer recommends 2 doses every 6 hours for 3 doses while some experts recommend only maintenance dosing as needed. It’s therefore probably safest to punt this to whatever poison control center or toxicologist you speak with.

Nachi: I feel like we are plugging the poison center a lot, but it’s such a good free, and usually very nice consult to have on your team.

Jeff: Nice consultant – what a win! Moving on to the cutting edge. There is a new Crotalidae antivenom called Crotalidae Immune F(ab’)2 or, more simply, Anavip. It should be available in the next few months. The dosing will be 10 vials up front over 60 minutes followed by an additional 10 vials if the symptoms having been controlled. 4 more vials may be given for symptom recurrence. Patients must be observed for a minimum of 18 hours after initial control of symptoms.

Nachi: This would be a really nice development as Anavip has a longer half life and therefore should reduce the rates of late coagulopathy and decrease the need for maintenance dosing, follow up, and repeating coags.

Jeff: And finally, like we mentioned before, injection of the trypsin has been tried as a bridge to antivenom, as has carbon monoxide, which may mediate degradation of fibrinogen dependent coagulation.

Nachi: Alright, so let’s talk about the disposition next. Victims of pit viper envenomations should be monitored for 8-12 hours from the time of the bite. They will need baseline labs and repeat testing ever 4-6 hours. IF there is no progression of the symptoms and repeat testing is normal, the patient can be discharged.

Jeff: Victims of coral snake bites should be admitted and observed for 12-24 hours regardless of symptoms.

Nachi: Victims of rattle snake envenomations who initially develop hematologic abnormalities and are treated with FabAV should have repeat testing done in 2-4 days and 5-7 days.

Jeff: Wounds should also be closely followed to avoid complications and long term disfigurement and disability. PT/OT may be necessary as well.

Nachi: Perfect, let’s round this episodes out with a review of the key points and clinical pearls from this month’s issue.

There are about 10,000 ED visits in the US for snake bites each year, and 1/3 of these involve venomous species.

In general, venomous snakes have a triangular or spade-like head, elliptical pupils, and hollow retractable fangs. In contrast, non-venemous snakes have a rounded head, round pupils, lack fangs, and can have a double row of vertical scales on the tail.

Venomous North American coral snakes often have adjacent red and yellow bands, whereas their nonvenomous counterparts usually have a characteristic black band between the red and yellow bands.

For prehospital care in the US, the following strategies are not recommended: incision or excision, use of venom extraction devices, tourniquets, chill methods, and electroshock therapy -- and they can all actually worsen outcomes. Prehospital providers should focus on rapid transport.

Be cognizant of compartment syndrome, but measure compartments when possible, as some envenomations present similarly but have only subcutaneous hypertension.

Neurologic effects can be delayed up to 12 hours after coral snake envenomations. Symptoms can include a descending paralysis.

For diagnostic testing, consider a CBC, coags, fibrinogen level, electrolytes, cpk, creatine, glucose, and urine studies. All patients with evenomation should be observed for at least 8 hours. Mark the site of envenomation circumferentially to monitor for changes.

Management of patients with snake bites should be treated with supportive care, pain control, and specific antivenom when indicated.

FabAV or CroFab is the antivenom of choice for pit viper envenomations. Although FabAV will reduce the duration and severity of symptoms and lab abnormalities, it will not reverse tissue necrosis and may not reverse neurologic effects.

Be aware of the possibility for a hypersensitivity reaction or serum sickness to FabAV. Treat with steroids, antihistamine, IV fluids, and epinephrine as appropriate.

Coral snake envenomations can be treated with NACSA, which halts or at least limits the progression of muscle paralysis and shortens the clinical course. Side effects to NACSA include dermal reaction as the most common -- and anaphylaxis as the most severe.

Patients with bites from exotic snakes should be monitored, likely in the ICU, for up to 24 hours as toxicity from some venom may have a delayed onset of up to 20 hours. You may have to turn to your local zoo for help with anti-venoms here.

Management of pregnant patient\s is the same as nonpregnant patients with regards to snake envenomations.

Dosing of antivenom is based on the amount of venom. Dosing is the same regardless of the age of the patient.

All patients requiring antivenom or with suspected envenomation should be admitted. Seek consultation with your regional poison center and local toxicologist

Jeff: So that wraps up the September 2018 episode of EMplify.

Nachi: As always - the address for this month’s credit is ebmedicine.net/E0918, so head over there right away to get your credit. Remember that the you heard throughout the episode corresponds to the answers to the CME questions.

Jeff: And don’t forget to grab your free issue of Synthetic Drug Intoxication in Children specifically for EMplify listeners. Feel free to share the link with your colleagues or through social media too. Next month we are talking sepsis and the ever frequently changing guidelines so it’s not something you want to miss. Talk to you soon.

8. *American College of Medical Toxicology, American Academy of Clinical Toxicology, American Association of Poison Control Centers, European Association of Poison Control Centres and Clinical Toxicologists, International Society on Toxinology, Asia Pacific Association of Medical Toxicology. Pressure immobilization after North American Crotalinae snake envenomation. Clin Toxicol (Phila). 2011;49(10):881-882. (Position statement)

About The Podcast

Get quick-hit summaries of hot topics in emergency medicine. EMplify summarizes evidence-based reviews in a monthly podcast. Highlights of the latest research published in EB Medicine's peer-reviewed journals educate and arm you for life in the ED.

Introduction

Points & Pearls

The Antivenom Dosing Algorithm is a unified treatment algorithm that was developed with the goal of quick identification and management of patients who may benefit from treatment with Crotalidae Polyvalent Immune Fab (CroFab®).

There is significant variability among patients with snake envenomations, and this algorithm does not represent a standard of care.

All cases of suspected or confirmed snake envenomation should be reported to Poison Control (1-800-222-1222).

Why and When to Use, and Next Steps

Why to Use

The Antivenom Dosing Algorithm is an anti-venom dosing tool for Crotalinae (pit viper, formerly known as Crotalidae) snake envenomations.

Antivenom is an extremely expensive resource that carries a risk of adverse events. Emergency clinicians should be aware of the indications for its use, as well as other steps to take in the management of patients with pit viper bites.

When to Use

Use the Antivenom Dosing Algorithm for patients with known or suspected Crotalinae envenomation.

This algorithm is not valid for snakebites on the head or neck, snakebites causing rhabdomyolysis, or in cases of anaphylaxis/anaphylactoid reactions to venom.

This algorithm does not apply to envenomation by coral snakes or any snakes that are not indigenous to the United States.

Next Steps

Maintenance therapy

Administer maintenance dosing of 2 vials of antivenom every 6 hours for 3 doses, at 6, 12, and 18 hours after initial control of symptoms is achieved.

Maintenance therapy may not be needed if close observation by a physician-expert is available.

Follow-up planning

The patient should return if swelling worsens and is not relieved by elevation; if abnormal bleeding occurs (eg, melena, gum bleeding, easy bruising); or if fever, rash, or muscle or joint pains occur (ie, symptoms suggesting serum sickness).

The patient should be given bleeding precautions: no contact sports, elective surgery, or dental work for 2 weeks.

The patient should be advised to follow up for repeat laboratory testing twice (at 2-3 days and 5-7 days after discharge), and then as needed.

Follow up as needed for cases in which antivenom was not administered or antivenom was administered for copperhead envenomation.

Calculator Review Author

Stephen A. Harding, MD

Henry J.N. Taub Department of Emergency Medicine

Baylor College of Medicine, Houston, TX

Advice

The leading edge of swelling and tenderness surrounding the envenomated area should be marked every 15 to 30 minutes. Elevate and immobilize the affected extremity, treat pain aggressively with intravenous opioids, and update the patient’s tetanus status as needed.

Critical Actions

The following should be avoided:

Cutting or suctioning the wound Ice

Nonsteroidal anti-inflammatory drugs

Prophylactic antibiotics

Prophylactic fasciotomy

Routine use of blood products

Electrical shock therapy

Steroids, unless allergic phenomena are observed

Tourniquets

Evidence Appraisal

Lavonas et al analyzed the medical literature regarding use of Crotalidae Polyvalent Immune Fab for pit viper envenomations. After analysis of 42 original articles, this panel of experts met and held a consensus-building meeting, which resulted in a unified treatment algorithm.

CME Information

Describe the evaluation, management, and disposition of patients presenting with envenomations from North American pit vipers and coral snakes.

List the indications, contraindications, and dosing for antivenom products for snakebites.

Manage anaphylactic and anaphylactoid reactions from venom and antivenom.

Identify and manage late or recurrent coagulopathy.

CME Information

Date of Original Release: September 1, 2018. Date of most recent review: August 10, 2018. Termination date: September 1, 2021.

Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the ACCME.

Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 4 Trauma CME and 1 Pharmacology CME credits

ACEP Accreditation: Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Category I credit per annual subscription.

AAFP Accreditation: This Enduring Material activity, Emergency Medicine Practice, has been reviewed and is acceptable for credit by the American Academy of Family Physicians. Term of approval begins 07/01/2018. Term of approval is for one year from this date. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Approved for 4 AAFP Prescribed credits.

AOA Accreditation: Emergency Medicine Practice is eligible for up to 48 American Osteopathic Association Category 2-A or 2-B credit hours per year.

Needs Assessment: The need for this educational activity was determined by a survey of medical staff, including the editorial board of this publication; review of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for emergency physicians.

Goals: Upon completion of this activity, you should be able to: (1) demonstrate medical decision-making based on the strongest clinical evidence; (2) cost-effectively diagnose and treat the most critical presentations; and (3) describe the most common medicolegal pitfalls for each topic covered.

Discussion of Investigational Information: As part of the journal, faculty may be presenting investigational information about pharmaceutical products that is outside Food and Drug Administration–approved labeling. Information presented as part of this activity is intended solely as continuing medical education and is not intended to promote off-label use of any pharmaceutical product.

Faculty Disclosures: It is the policy of EB Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to complete a full disclosure statement.The information received is as follows: Dr. Sheikh, Dr. Leffers, Dr. Sessions, Dr. Mishler, Dr. Toscano, and their related parties report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation. Dr. Jagoda made the following disclosures: Consultant, Daiichi Sankyo Inc; Consultant, Pfizer Inc; Consultant, Banyan Biomarkers Inc; Consulting fees, EB Medicine.

Commercial Support: This issue of Emergency Medicine Practice did not receive any commercial support.

Earning Credit: Two Convenient Methods: (1) Go online to www.ebmedicine.net/CME and click on the title of the article. (2) Mail or fax the CME Answer And Evaluation Form (included with your June and December issues) to EB Medicine.

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